2w80: Difference between revisions

Latest revision as of 07:48, 9 October 2024

Structure of a complex between Neisseria meningitidis factor H binding protein and CCPs 6-7 of human complement factor H

Structural highlights

2w80 is a 8 chain structure with sequence from Homo sapiens and Neisseria meningitidis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.35Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FHBP_NEIMB A bacterial surface lipoprotein that binds host (human) complement factor H (fH, gene CFH), binding contributes to the avoidance of complement-mediated lysis by N.meningitidis. Binding of fH to the bacteria surface is independent of bacterial sialic acid moieties (PubMed:16751403). fH binding affinity is high enough that it may sequester plasma fH, depleting its circulating levels and de-regulating complement in the host (Probable). This protein induces high levels of bactericidal antibodies in mice (PubMed:12642606, PubMed:15039331, PubMed:15664958, PubMed:21753121, PubMed:23133374).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The complement system is an essential component of the innate and acquired immune system, and consists of a series of proteolytic cascades that are initiated by the presence of microorganisms. In health, activation of complement is precisely controlled through membrane-bound and soluble plasma-regulatory proteins including complement factor H (fH; ref. 2), a 155 kDa protein composed of 20 domains (termed complement control protein repeats). Many pathogens have evolved the ability to avoid immune-killing by recruiting host complement regulators and several pathogens have adapted to avoid complement-mediated killing by sequestering fH to their surface. Here we present the structure of a complement regulator in complex with its pathogen surface-protein ligand. This reveals how the important human pathogen Neisseria meningitidis subverts immune responses by mimicking the host, using protein instead of charged-carbohydrate chemistry to recruit the host complement regulator, fH. The structure also indicates the molecular basis of the host-specificity of the interaction between fH and the meningococcus, and informs attempts to develop novel therapeutics and vaccines.

Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates.,Schneider MC, Prosser BE, Caesar JJ, Kugelberg E, Li S, Zhang Q, Quoraishi S, Lovett JE, Deane JE, Sim RB, Roversi P, Johnson S, Tang CM, Lea SM Nature. 2009 Apr 16;458(7240):890-3. Epub 2009 Feb 18. PMID:19225461^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Masignani V, Comanducci M, Giuliani MM, Bambini S, Adu-Bobie J, Arico B, Brunelli B, Pieri A, Santini L, Savino S, Serruto D, Litt D, Kroll S, Welsch JA, Granoff DM, Rappuoli R, Pizza M. Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870. J Exp Med. 2003 Mar 17;197(6):789-99. PMID:12642606 doi:10.1084/jem.20021911
↑ Fletcher LD, Bernfield L, Barniak V, Farley JE, Howell A, Knauf M, Ooi P, Smith RP, Weise P, Wetherell M, Xie X, Zagursky R, Zhang Y, Zlotnick GW. Vaccine potential of the Neisseria meningitidis 2086 lipoprotein. Infect Immun. 2004 Apr;72(4):2088-100. PMID:15039331 doi:10.1128/IAI.72.4.2088-2100.2004
↑ Giuliani MM, Santini L, Brunelli B, Biolchi A, Aricò B, Di Marcello F, Cartocci E, Comanducci M, Masignani V, Lozzi L, Savino S, Scarselli M, Rappuoli R, Pizza M. The region comprising amino acids 100 to 255 of Neisseria meningitidis lipoprotein GNA 1870 elicits bactericidal antibodies. Infect Immun. 2005 Feb;73(2):1151-60. PMID:15664958 doi:10.1128/IAI.73.2.1151-1160.2005
↑ Schneider MC, Exley RM, Chan H, Feavers I, Kang YH, Sim RB, Tang CM. Functional significance of factor H binding to Neisseria meningitidis. J Immunol. 2006 Jun 15;176(12):7566-75. PMID:16751403 doi:10.4049/jimmunol.176.12.7566
↑ Scarselli M, Arico B, Brunelli B, Savino S, Di Marcello F, Palumbo E, Veggi D, Ciucchi L, Cartocci E, Bottomley MJ, Malito E, Lo Surdo P, Comanducci M, Giuliani MM, Cantini F, Dragonetti S, Colaprico A, Doro F, Giannetti P, Pallaoro M, Brogioni B, Tontini M, Hilleringmann M, Nardi-Dei V, Banci L, Pizza M, Rappuoli R. Rational design of a meningococcal antigen inducing broad protective immunity. Sci Transl Med. 2011 Jul 13;3(91):91ra62. PMID:21753121 doi:10.1126/scitranslmed.3002234
↑ Johnson S, Tan L, van der Veen S, Caesar J, Goicoechea De Jorge E, Harding RJ, Bai X, Exley RM, Ward PN, Ruivo N, Trivedi K, Cumber E, Jones R, Newham L, Staunton D, Ufret-Vincenty R, Borrow R, Pickering MC, Lea SM, Tang CM. Design and Evaluation of Meningococcal Vaccines through Structure-Based Modification of Host and Pathogen Molecules. PLoS Pathog. 2012 Oct;8(10):e1002981. doi: 10.1371/journal.ppat.1002981. Epub, 2012 Oct 25. PMID:23133374 doi:https://dx.doi.org/10.1371/journal.ppat.1002981
↑ Schneider MC, Prosser BE, Caesar JJ, Kugelberg E, Li S, Zhang Q, Quoraishi S, Lovett JE, Deane JE, Sim RB, Roversi P, Johnson S, Tang CM, Lea SM. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature. 2009 Apr 16;458(7240):890-3. Epub 2009 Feb 18. PMID:19225461 doi:10.1038/nature07769
↑ Schneider MC, Prosser BE, Caesar JJ, Kugelberg E, Li S, Zhang Q, Quoraishi S, Lovett JE, Deane JE, Sim RB, Roversi P, Johnson S, Tang CM, Lea SM. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature. 2009 Apr 16;458(7240):890-3. Epub 2009 Feb 18. PMID:19225461 doi:10.1038/nature07769

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Masignani V, Comanducci M, Giuliani MM, Bambini S, Adu-Bobie J, Arico B, Brunelli B, Pieri A, Santini L, Savino S, Serruto D, Litt D, Kroll S, Welsch JA, Granoff DM, Rappuoli R, Pizza M. Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870. J Exp Med. 2003 Mar 17;197(6):789-99. PMID:12642606 doi:10.1084/jem.20021911

[2] Fletcher LD, Bernfield L, Barniak V, Farley JE, Howell A, Knauf M, Ooi P, Smith RP, Weise P, Wetherell M, Xie X, Zagursky R, Zhang Y, Zlotnick GW. Vaccine potential of the Neisseria meningitidis 2086 lipoprotein. Infect Immun. 2004 Apr;72(4):2088-100. PMID:15039331 doi:10.1128/IAI.72.4.2088-2100.2004

[3] Giuliani MM, Santini L, Brunelli B, Biolchi A, Aricò B, Di Marcello F, Cartocci E, Comanducci M, Masignani V, Lozzi L, Savino S, Scarselli M, Rappuoli R, Pizza M. The region comprising amino acids 100 to 255 of Neisseria meningitidis lipoprotein GNA 1870 elicits bactericidal antibodies. Infect Immun. 2005 Feb;73(2):1151-60. PMID:15664958 doi:10.1128/IAI.73.2.1151-1160.2005

[4] Schneider MC, Exley RM, Chan H, Feavers I, Kang YH, Sim RB, Tang CM. Functional significance of factor H binding to Neisseria meningitidis. J Immunol. 2006 Jun 15;176(12):7566-75. PMID:16751403 doi:10.4049/jimmunol.176.12.7566

[5] Scarselli M, Arico B, Brunelli B, Savino S, Di Marcello F, Palumbo E, Veggi D, Ciucchi L, Cartocci E, Bottomley MJ, Malito E, Lo Surdo P, Comanducci M, Giuliani MM, Cantini F, Dragonetti S, Colaprico A, Doro F, Giannetti P, Pallaoro M, Brogioni B, Tontini M, Hilleringmann M, Nardi-Dei V, Banci L, Pizza M, Rappuoli R. Rational design of a meningococcal antigen inducing broad protective immunity. Sci Transl Med. 2011 Jul 13;3(91):91ra62. PMID:21753121 doi:10.1126/scitranslmed.3002234

[6] Johnson S, Tan L, van der Veen S, Caesar J, Goicoechea De Jorge E, Harding RJ, Bai X, Exley RM, Ward PN, Ruivo N, Trivedi K, Cumber E, Jones R, Newham L, Staunton D, Ufret-Vincenty R, Borrow R, Pickering MC, Lea SM, Tang CM. Design and Evaluation of Meningococcal Vaccines through Structure-Based Modification of Host and Pathogen Molecules. PLoS Pathog. 2012 Oct;8(10):e1002981. doi: 10.1371/journal.ppat.1002981. Epub, 2012 Oct 25. PMID:23133374 doi:https://dx.doi.org/10.1371/journal.ppat.1002981

[7] Schneider MC, Prosser BE, Caesar JJ, Kugelberg E, Li S, Zhang Q, Quoraishi S, Lovett JE, Deane JE, Sim RB, Roversi P, Johnson S, Tang CM, Lea SM. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature. 2009 Apr 16;458(7240):890-3. Epub 2009 Feb 18. PMID:19225461 doi:10.1038/nature07769

[8] Schneider MC, Prosser BE, Caesar JJ, Kugelberg E, Li S, Zhang Q, Quoraishi S, Lovett JE, Deane JE, Sim RB, Roversi P, Johnson S, Tang CM, Lea SM. Neisseria meningitidis recruits factor H using protein mimicry of host carbohydrates. Nature. 2009 Apr 16;458(7240):890-3. Epub 2009 Feb 18. PMID:19225461 doi:10.1038/nature07769

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[2]

[3]

[4]

[5]

[6]

[7]

[8]

@@ Line 7: / Line 7: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2w80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w80 OCA], [https://pdbe.org/2w80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w80 RCSB], [https://www.ebi.ac.uk/pdbsum/2w80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w80 ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[https://www.uniprot.org/uniprot/CFAH_HUMAN CFAH_HUMAN] Genetic variations in CFH are associated with basal laminar drusen (BLD) [MIM:[https://omim.org/entry/126700 126700]; also known as drusen of Bruch membrane or cuticular drusen or grouped early adult-onset drusen. Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. Basal laminar drusen refers to an early adult-onset drusen phenotype that shows a pattern of uniform small, slightly raised yellow subretinal nodules randomly scattered in the macula. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss.  Defects in CFH are the cause of complement factor H deficiency (CFHD) [MIM:[https://omim.org/entry/609814 609814]. A disorder that can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. Laboratory features usually include decreased serum levels of factor H, complement component C3, and a decrease in other terminal complement components, indicating activation of the alternative complement pathway. It is associated with a number of renal diseases with variable clinical presentation and progression, including membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome.<ref>PMID:9312129</ref> <ref>PMID:10803850</ref> <ref>PMID:11170895</ref> <ref>PMID:11170896</ref> <ref>PMID:11158219</ref> <ref>PMID:12020532</ref> <ref>PMID:14978182</ref> <ref>PMID:16612335</ref>   Defects in CFH are a cause of susceptibility to hemolytic uremic syndrome atypical type 1 (AHUS1) [MIM:[https://omim.org/entry/235400 235400]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:14978182</ref> <ref>PMID:9551389</ref> <ref>PMID:10577907</ref> <ref>PMID:10762557</ref> <ref>PMID:11851332</ref> <ref>PMID:14583443</ref> <ref>PMID:12960213</ref> <ref>PMID:20513133</ref>   Genetic variation in CFH is associated with age-related macular degeneration type 4 (ARMD4) [MIM:[https://omim.org/entry/610698 610698]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:22019782</ref>
 == Function ==
-[https://www.uniprot.org/uniprot/CFAH_HUMAN CFAH_HUMAN] Factor H functions as a cofactor in the inactivation of C3b by factor I and also increases the rate of dissociation of the C3bBb complex (C3 convertase) and the (C3b)NBB complex (C5 convertase) in the alternative complement pathway.
+[https://www.uniprot.org/uniprot/FHBP_NEIMB FHBP_NEIMB] A bacterial surface lipoprotein that binds host (human) complement factor H (fH, gene CFH), binding contributes to the avoidance of complement-mediated lysis by N.meningitidis. Binding of fH to the bacteria surface is independent of bacterial sialic acid moieties (PubMed:16751403). fH binding affinity is high enough that it may sequester plasma fH, depleting its circulating levels and de-regulating complement in the host (Probable). This protein induces high levels of bactericidal antibodies in mice (PubMed:12642606, PubMed:15039331, PubMed:15664958, PubMed:21753121, PubMed:23133374).<ref>PMID:12642606</ref> <ref>PMID:15039331</ref> <ref>PMID:15664958</ref> <ref>PMID:16751403</ref> <ref>PMID:21753121</ref> <ref>PMID:23133374</ref> <ref>PMID:19225461</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 16: / Line 14: @@
    <jmolCheckbox>
      <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w8/2w80_consurf.spt"</scriptWhenChecked>
-     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
    </jmolCheckbox>

2w80: Difference between revisions

Latest revision as of 07:48, 9 October 2024

Structure of a complex between Neisseria meningitidis factor H binding protein and CCPs 6-7 of human complement factor H

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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